Department of Pharmacology, Seoul National University College of Medicine, Seoul 03080, Korea.
Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, Seoul 03080, Korea.
Cells. 2020 Mar 15;9(3):722. doi: 10.3390/cells9030722.
Constitutively activated STAT3 plays an essential role in the initiation, progression, maintenance, malignancy, and drug resistance of cancer, including glioblastoma, suggesting that STAT3 is a potential therapeutic target for cancer therapy. We recently identified ODZ10117 as a small molecule inhibitor of STAT3 and suggested that it may have an effective therapeutic utility for the STAT3-targeted cancer therapy. Here, we demonstrated the therapeutic efficacy of ODZ10117 in glioblastoma by targeting STAT3. ODZ10117 inhibited migration and invasion and induced apoptotic cell death by targeting STAT3 in glioblastoma cells and patient-derived primary glioblastoma cells. In addition, ODZ10117 suppressed stem cell properties in glioma stem cells (GSCs). Finally, the administration of ODZ10117 showed significant therapeutic efficacy in mouse xenograft models of GSCs and glioblastoma cells. Collectively, ODZ10117 is a promising therapeutic candidate for glioblastoma by targeting STAT3.
组成性激活的 STAT3 在癌症（包括胶质母细胞瘤）的发生、进展、维持、恶性转化和耐药性中发挥重要作用，提示 STAT3 是癌症治疗的潜在治疗靶点。我们最近鉴定出 ODZ10117 是 STAT3 的小分子抑制剂，并提出它可能对 STAT3 靶向癌症治疗具有有效的治疗用途。在这里，我们通过靶向 STAT3 证明了 ODZ10117 在胶质母细胞瘤中的治疗功效。ODZ10117 通过靶向 STAT3 抑制胶质母细胞瘤细胞和患者来源的原发性胶质母细胞瘤细胞的迁移和侵袭，并诱导细胞凋亡。此外，ODZ10117 抑制了神经胶质瘤干细胞（GSCs）中的干细胞特性。最后，ODZ10117 的给药在 GSCs 和胶质母细胞瘤细胞的小鼠异种移植模型中显示出显著的治疗功效。总之，ODZ10117 通过靶向 STAT3 是一种有前途的胶质母细胞瘤治疗候选药物。
